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基于比敏康合剂治疗变应性鼻炎作用的分子机制:网络药理学和 RNA 测序分析。

Molecular Mechanisms Underlying the Effects of Bimin Kang Mixture on Allergic Rhinitis: Network Pharmacology and RNA Sequencing Analysis.

机构信息

The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, China.

Department of Otorhinolaryngology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250014, China.

出版信息

Biomed Res Int. 2022 Oct 28;2022:7034078. doi: 10.1155/2022/7034078. eCollection 2022.

Abstract

BACKGROUND

Allergic rhinitis (AR) is a highly prevalent chronic inflammatory disease of the respiratory tract. Previous studies have demonstrated that Bimin Kang Mixture (BMK) is effective in alleviating AR symptoms and reducing the secretion of inflammatory factors and mucin; however, the precise mechanisms underlying these effects remain unclear.

METHODS

We built target networks for each medication component using a network pharmacology technique and used RNA-seq transcriptome analysis to screen differentially expressed genes (DEGs) for AR patients and control groups. The overlapping targets in the two groups were assessed using PPI networks, GO, and KEGG enrichment analyses. The binding ability of essential components to dock with hub target genes was investigated using molecular docking. Finally, we demonstrate how BMK can treat AR by regulating the NF-B signaling pathway through animal experiments.

RESULTS

Effective targets from network pharmacology were combined with DEGs from RNA-seq, with 20 intersections as key target genes. The construction of the PPI network finally identified 5 hub target genes, and all hub target genes were in the NF-B signaling pathway. Molecular docking suggests that citric acid, deoxyandrographolide, quercetin, luteolin, and kaempferol are structurally stable and can spontaneously attach to IL-1, CXCL2, CXCL8, CCL20, and PTGS2 receptors. Animal experiments have shown that BMK inhibits NF-B transcription factor activation, reduces the expression of proinflammatory cytokines and chemokines IL-1, CXCL2, IL-8, and COX-2, and exerts anti-inflammatory and anti-allergic effects.

CONCLUSION

BMK by regulating the NF-B signaling pathway improves inflammatory cell infiltration, regulates mucosal immune balance, and reduces airway hypersensitivity. These findings provide theoretical support for the clinical efficacy of BMK for AR treatment.

摘要

背景

变应性鼻炎(AR)是一种高发的呼吸道慢性炎症性疾病。既往研究表明痹敏康合剂(BMK)可有效缓解 AR 症状,减少炎症因子和黏蛋白的分泌,但确切作用机制尚不清楚。

方法

采用网络药理学技术构建各药物成分的靶标网络,利用 RNA-seq 转录组分析筛选 AR 患者与对照组的差异表达基因(DEGs),通过 PPI 网络、GO、KEGG 富集分析评估两组的重叠靶标,采用分子对接研究关键成分与枢纽靶基因的结合能力,最后通过动物实验证实 BMK 如何通过调控 NF-B 信号通路治疗 AR。

结果

网络药理学的有效靶点与 RNA-seq 的 DEGs 结合,取 20 个交集作为关键靶基因。构建 PPI 网络最终确定了 5 个枢纽靶基因,所有枢纽靶基因均位于 NF-B 信号通路中。分子对接表明柠檬酸、去氧穿心莲内酯、槲皮素、木樨草素和山奈酚结构稳定,可自发与 IL-1、CXCL2、CXCL8、CCL20 和 PTGS2 受体结合。动物实验表明,BMK 可抑制 NF-B 转录因子激活,降低促炎细胞因子和趋化因子 IL-1、CXCL2、IL-8 和 COX-2 的表达,发挥抗炎和抗过敏作用。

结论

BMK 通过调控 NF-B 信号通路改善炎症细胞浸润,调节黏膜免疫平衡,降低气道高反应性,为 BMK 治疗 AR 的临床疗效提供理论支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d88/9635970/f127b1bab98a/BMRI2022-7034078.001.jpg

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